Nuclear magnetic resonance imaging (MRI) is an important modality for both clinical and basic-science imaging applications. A recent notable advance in MRI was the introduction of the “hyperpolarized” noble gases helium-3 (3He) and xenon-129 (129Xe) as novel magnetic-resonance contrast agents [1]. Nuclear polarization levels approaching 100 percent can be achieved using hyperpolarized noble gases, and this dramatic increase in the polarization compared to that typically achieved at thermal equilibrium (at most approximately 10−4) has presented the opportunity for many new MRI applications. For example, high-resolution MR images of the lung air spaces have been demonstrated following the inhalation of hyperpolarized-3He gas [2–5], and studies suggest that 3He lung imaging shows promise for differentiating healthy lungs from those with pathologies such as chronic obstructive pulmonary disease [6,7], asthma [8] and cystic fibrosis [9].
Achieving a high signal-to-noise ratio (SNR) through optimization of the MRI acquisition method (that is, the “pulse sequence”) has long been a fundamental goal in the development of MRI because the thermal-equilibrium nuclear magnetic resonance signal is inherently weak. Although hyperpolarized gases intrinsically provide a large nuclear polarization, the SNR performance of the associated pulse sequences is still of prime concern because hyperpolarized gases are expensive to prepare and, in the case of 3He, are in limited world supply. Therefore, MRI pulse sequences for hyperpolarized-gas imaging that provide high SNR of are significant practical importance. Furthermore, since the hyperpolarized magnetization is inherently in a non-equilibrium state, the lifetime of the hyperpolarized state (as measured by the T1 relaxation time) is limited, for many practical applications to 10–100 seconds, and thus applicable MRI pulse sequences should also acquire the image data rapidly.
In the case of sufficiently long T2 relaxation times, it is well established in conventional proton (1H) MRI that pulse sequences which maintain the phase coherence of at least a significant fraction of the transverse magnetization during the application of successive radio-frequency (RF) pulses are useful for rapid, high-SNk magnetic resonance imaging. Examples of such techniques commonly used for 1H MRI include RARE imaging [10] and its derivatives such as HASTE [11], and FISP imaging [12]. However, the application of these established techniques for rapid, high-SNR hyperpolarized-gas imaging is limited due to diffusion-induced signal attenuation that results from the diffusion of the gas in the magnetic-field gradients required for imaging and those progresses during data acquisition. (The diffusivities of the free gases are approximately 104–105 larger than that for water protons in the body of an animal or human.) The degree of signal attenuation increases with decreasing voxel size (that is, increasing spatial resolution) and thus the spatial resolution is limited by the associated image blurring that result from the progressive signal attenuation during data acquisition.
A recently published study that investigated the use of RARE-type pulse sequences for hyperpolarized 3He MRI of the human lung claimed, based on theoretical analysis and corresponding experimental results, that the diffusion-dependent resolution limit for RARE-type techniques is 6 mm [13]. In contrast, transverse-magnetization-spoiled, gradient-echo-based MRI pulse sequences currently used for hyperpolarized-gas imaging of the human lung typically use an in-plane resolution of approximately 3 mm, and higher spatial resolution may certainly be needed for other or future applications of hyperpolarized gases. Nonetheless, for hyperpolarized-gas imaging, these spoiled, gradient-echo-based MRI pulse sequences yield (for equal spatial resolution) only approximately one-tenth of the signal that could be provided by a RARE-type pulse sequence if the diffusion-induced signal attenuation during the RARE-type pulse sequence could be made to be negligible.
Therefore, it would clearly be of significant practical importance if it were possible to appropriately optimize pulse sequences that maintain the phase coherence of at least a significant fraction of the transverse magnetization during the application of successive RF pulses to minimize diffusion-induced signal attenuation and therefore permit the SNR advantage of these techniques to be realized for hyperpolarized-gas imaging in conjunction with higher spatial resolution. This SNR increase can be traded for substantially lower dose, and hence much lower cost, of the hyperpolarized-gas contrast agent. In addition to in-vivo hyperpolarized gas imaging, such optimized techniques would potentially also be useful for non-biological applications of hyperpolarized gases, for example material science studies, as well as for magnetic resonance imaging of any other gas for biological or non-biological applications. These optimized techniques could also serve as the foundation for a variety of specialized gas-imaging pulse sequences, such as those for apparent-diffusion-coefficient [14] or dynamic [15] imaging.